論文ID: JJID.2017.068
The pharmacokinetic-pharmacodynamic (PK-PD) breakpoints (BPs) of garenoxacin (GRNX) and other oral quinolones were calculated using the Monte Carlo simulation (MCS) based on the distribution of changes in their plasma concentrations. PK-PD BPs of 400 mg once a day (QD) of GRNX for the free area under the curve/minimum inhibitory concentration (fAUC/MIC) for 30 of Streptococcus pneumoniae and 100 of Gram–negative bacteria: (G (–)) were 0.5 and 0.125 μg/mL, respectively. PK-PD BPs of other quinolones for S. pneumoniae/G(–) were 1/0.25 μg/mL for levofloxacin (LVFX) 500 mg QD, 0.5/0.125 μg/mL for moxifloxacin (MFLX) 400 mg QD, 0.0625/0.0156 μg/mL for sitafloxacin (STFX) 50 mg twice a day (BID) (100 mg QD), and 0.125/0.0313 μg/mL for STFX 100 mg BID. We also investigated hypothetical probability of target attainments (PTAs) of fAUC/MIC for community-acquired pneumonia (CAP) using MCS, in consideration of isolation frequencies of three main causative pathogens of CAP; S. pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. As for PTA against hypothetical CAP in adults, PTA of fAUC/MIC was 100% with GRNX and MFLX, 96–97% with STFX at 100 mg BID, 45–46% with LVFX, and 53-58% with STFX at 100 mg QD and 50 mg BID. Based on the PK-PD BP, GRNX showed higher fAUC/MIC than the other quinolones tested against three main pathogens of respiratory infections.
